Photodynamic therapy using a photosensitizer has attracted attention as a form of therapy capable of overcoming sequelae of cancer and side effects of conventional cancer treatments such as surgery, radiation therapy, and drug therapy.
The photosensitizer is excited by irradiation with light at a specific wavelength, and reacts with a surrounding substrate or oxygen, thereby producing a reactive oxygen species, resulting in apoptosis or necrosis of surrounding tumor cells.
However, a first generation photosensitizer currently used for caner treatment, Photofrin, has two major disadvantages, which are a low molar absorption coefficient of 1170 M−1 cm−1 at a wavelength of 630 nm, and a more than 6-week-lasting side effect of skin photosensitivity. Skin photosensitivity refers to a side effect of killing normal cells of skin or eyes of a patient by photosensitizers non-specifically accumulated and remaining after administration of the photosensitizer when the patient is exposed to light. Since Photofrin is easily accumulated non-specifically in cells of the skin or eyes due to hydrophobicity, it is known that the side effect of skin photosensitivity lasts relatively long.
To overcome the disadvantages of Photofrin, a second generation photosensitizer, Foscan, has been developed. Foscan has a high molar absorption coefficient of 30000 M−1 cm−1 at 652 nm, and thus exhibits a 200-fold increase in efficiency of the photodynamic therapy, compared to Photofrin. However, since Foscan also has hydrophobicity, it is not able to significantly reduce the side effect of the skin photosensitivity.
To overcome such a side effect of the skin photosensitivity, a hydrophilic second generation photosensitizer, mono-L-aspartyl chlorine e6 (NPe6), which is in phase III clinical trial, has been developed. Mono-L-aspartyl chlorine e6 is a photosensitizer to which four carboxyl groups are introduced, which greatly reduces the duration of the side effect of the skin photosensitivity to 1 week because of the hydrophilicity of the carboxyl groups. However, the photosensitizer having the carboxyl groups is negatively charged and difficult to be taken up into cancer cells even upon reaching a cancer tissue. Moreover, the photosensitizer having the hydrophilic carboxyl group can be excreted rapidly from a body through the urinary system. Accordingly, to be accumulated in a tumor tissue in an appropriate concentration, the hydrophilic photosensitizer should be administered at a much higher dose than the hydrophobic photosensitizer. As a result, an amount of the photosensitizer non-specifically accumulated in the normal tissue cannot be reduced to a satisfactory level, and thus the second generation hydrophilic photosensitizer still has the side effect of the skin photosensitivity.